Moving past "think local, act global": A perspective on geographic disparity.

The transplant community has debated the necessity and merits of broader organ distribution for several years, but the debate has been fundamentally shaped by inaccurate assessments of donor supply and demand. The possible legal requirements of distribution must be balanced with (a) the moral and statutory imperatives to reduce inequities resulting from socioeconomic disparity, and (b) the shortcomings of MELD in predicting mortality risk in rural areas. In this viewpoint, we use the example of liver transplantation to discuss the drivers of geographic disparity as a direct consequence of donation rates, local organ use, wealth, and poverty. Seen in this light, strategies seeking to equalize MELD at transplant across the United States risk severely exacerbating existing inequalities in access to health care.

Disparities in Access to Liver Transplant Referral and Evaluation among Patients with Hepatocellular Carcinoma in Georgia.

Liver transplantation offers the best survival for patients with early-stage hepatocellular carcinoma (HCC). Prior studies have demonstrated disparities in transplant access; none have examined the early steps of the transplant process. We identified determinants of access to transplant referral and evaluation among patients with HCC with a single tumor either within Milan or meeting downstaging criteria in Georgia.Population-based cancer registry data from 2010 to 2019 were linked to liver transplant centers in Georgia. Primary cohort: adult patients with HCC with a single tumor ≤8 cm in diameter, no extrahepatic involvement, and no vascular involvement. Secondary cohort: primary cohort plus patients with multiple tumors confined to one lobe. We estimated time to transplant referral, evaluation initiation, and evaluation completion, accounting for the competing risk of death. In sensitivity analyses, we also accounted for non-transplant cancer treatment.Among 1,379 patients with early-stage HCC in Georgia, 26% were referred to liver transplant. Private insurance and younger age were associated with increased likelihood of referral, while requiring downstaging was associated with lower likelihood of referral. Patients living in census tracts with ≥20% of residents in poverty were less likely to initiate evaluation among those referred [cause-specific hazard ratio (csHR): 0.62, 95% confidence interval (CI): 0.42-0.94]. Medicaid patients were less likely to complete the evaluation once initiated (csHR: 0.53, 95% CI: 0.32-0.89).Different sociodemographic factors were associated with each stage of the transplant process among patients with early-stage HCC in Georgia, emphasizing unique barriers to access and the need for targeted interventions at each step. SIGNIFICANCE: Among patients with early-stage HCC in Georgia, age and insurance type were associated with referral to liver transplant, race, and poverty with evaluation initiation, and insurance type with evaluation completion. Opportunities to improve transplant access include informing referring providers about insurance requirements, addressing barriers to evaluation initiation, and streamlining the evaluation process.

PKI-587 and sorafenib alone and in combination on inhibition of liver cancer stem cell proliferation.

BACKGROUND: Deregulated Ras/Raf/mitogen-activated protein kinase and PI3 K/AKT/mTOR signaling pathways are significant in hepatocellular carcinoma proliferation (HCC). In this study we evaluated differences in the antiproliferative effect of dual PI3 K/Akt/mTOR and Ras/Raf/mitogen-activated protein kinase inhibition of non liver cancer stem cell lines (PLC and HuH7) and liver cancer stem cell (LCSC) lines (CD133, CD44, CD24, and aldehyde dehydrogenase 1-positive cells). MATERIALS AND METHODS: Flow cytometry was performed on the resulting tumors to identify the LCSC markers CD133, CD44, CD24, and aldehyde dehydrogenase 1. Methylthiazol tetrazolium assay was used to assess cellular proliferation. Finally, a Western blot assay was used to evaluate for inhibition of specific enzymes in these two signaling pathways. RESULTS: Using flow cytometry, we found that LCSC contain 64.4% CD133 + cells, 83.2% CD44 + cells, and 96.4% CD24 + cells. PKI-587 and sorafenib caused inhibiton of LCSC and HCC cell proliferation. PLC cells were more sensitive to PKI-587 than LCSC or Huh7 (P < 0.001). Interestingly, HuH7 cells were more sensitive to sorafenib than LCSC or PLC cells. Additionally, combination therapy with PKI-587 and sorafenib caused significantly more inhibition than monotherapy in HuH7, PLC, and LCSC. Using the methylthiazol tetrazolium assay, we found that the LCSC proliferation was inhibited with sorafenib monotherapy 39% at 5 µM (P < 0.001; n = 12) and 67% by PKI-587 at 0.1 µM (P = 0.002, n = 12) compared with control. The combination of PKI-587 and sorafenib, however, synergistically inhibited LCSC proliferation by 86% (P = 0.002; n = 12). CONCLUSIONS: LCSC (CD133+, CD44+, CD24+) were able to develop very aggressive tumors with low cell concentrations at 4 to 6 wk. Cells CD133+, CD44+, CD24+, which demonstrated at least moderate resistance to therapy in vitro. The combination of PKI-587 and sorafenib was better than either drug alone at inhibiting of LCSC and on HCC cell proliferation.

Risk factors for venous thromboembolism in patients with chronic liver disease.

BACKGROUND: Pharmacologic prophylaxis for venous thromboembolism (VTE) in patients with chronic liver disease (CLD) presents a unique challenge because of coagulopathies associated with the disease. When evaluating whether these patients require VTE prophylaxis upon hospitalization, it would be advantageous if risk factors for the development of VTE in this population were known. OBJECTIVE: To evaluate risk factors associated with the development of VTE in patients with CLD. METHODS: A retrospective case-control study was conducted. Patients admitted to the University of Kentucky Chandler Hospital from October 2006 to July 2010 with a diagnosis of CLD and VTE were matched in a 1:3 fashion with CLD patients without VTE. The primary objective was to determine whether there were significant differences in laboratory values between the 2 groups. RESULTS: During this time, 27 patients with CLD (1.0%) were diagnosed with VTE. These patients had significantly lower median aspartate aminotransferase (AST) (47 vs 70 U/L, p = 0.04), alanine transaminase (ALT) (24.5 vs 36 U/L, p = 0.02), albumin (2.1 vs 2.4 g/dL, p = 0.02) and hematocrit (Hct) (28.3% vs 32%, p = 0.03) values compared to the control patients. Patients with albumin lower than 1.9 g/dL had a 5.1 times greater risk of VTE compared to patients with albumin of 2.8 g/dL and higher (OR 5.14, 95% CI 1.05-25.2). CONCLUSIONS: Patients with CLD who developed VTE had significantly lower AST, ALT, albumin, and Hct compared to those of control patients. Studies are necessary to further examine the significance of this finding.

Peri-operative challenges and long-term outcomes in liver transplantation for polycystic liver disease.

BACKGROUND: The purpose of this study was to determine peri-operative mortality and long-term outcomes in patients undergoing liver transplantation in the US using the United Network for Organ Sharing (UNOS) database. METHODS: This study is a retrospective review of liver transplantations (LT) recorded in the UNOS database performed between 1988 and 2010. In total, 107 411 LT were performed in the US, 357 (0.3%) were for adult polycystic liver disease (PLD). A random group of 9416 adult patients transplanted for other diagnoses was created for comparison (10% of the adult non-PLD database). RESULTS: Two hundred and seventy-one patients in the adult PLD group were females (75.9%), the mean age was 52.3 ± 8.2 [standard deviation (SD)] years. The median length of transplantation hospital stay was 11 days (interquartile range 8-21). Patients from the PLD group versus the comparison group (9416 patients) consisted of more females, lower Model for End-Stage Liver Disease (MELD) scores (17 versus 21 points), more multi-organ transplants (41% versus 4 %), chronic renal failure (creatinine 2.7 versus 1.5) and fewer patients with chronic hepatitis C (1.4% versus 32%). Peri-operative mortality (≤30 days) was 9% in the PLD versus 6% in the comparison group; however, at 1 year PLD survival was similar (85% versus 85%) to other diagnoses and better at 3 (81% versus 77%) and 5 years (77% versus 71%, overall Log Rank P = 0.006). A similar PLD survival advantage was observed in isolated initial transplants (P = 0.019). CONCLUSION: In spite of early technical challenges and mortality, transplantation should be considered an option for selected patients with PLD as excellent long-term outcomes can be achieved.

PKI-587 and sorafenib targeting PI3K/AKT/mTOR and Ras/Raf/MAPK pathways synergistically inhibit HCC cell proliferation.

BACKGROUND: Deregulated Ras/Raf/MAPK and PI3K/AKT/mTOR signaling pathways are found in hepatocellular carcinoma (HCC). This study aimed to test the inhibitory effects of PKI-587 and sorafenib as single agents or in combination on HCC (Huh7 cell line) proliferation. MATERIALS AND METHODS: (3)H-thymidine incorporation and MTT assay were used to assess Huh7 cell proliferation. Phosphorylation of the key enzymes in the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways was detected by Western blot. RESULTS: We found that PKI-587 is a more potent PI3K/mTOR inhibitor than PI-103. Combination of PKI-587 and sorafenib was a more effective inhibitor of Huh7 proliferation than the combination of PI-103 and sorafenib. Combination of PKI-587 and sorafenib synergistically inhibited epidermal growth factor (EGF)-stimulated Huh7 proliferation compared with monodrug therapy. EGF increased phosphorylation of Ras/Raf downstream signaling proteins MEK and ERK; EGF-stimulated activation was inhibited by sorafenib. However, sorafenib, as a single agent, increased AKT (Ser473) phosphorylation. EGF-stimulated AKT (ser473) activation was inhibited by PKI-587. PKI-587 is a potent inhibitor of AKT (Ser473), mTOR (Ser2448), and S6K (Thr389) phosphorylation; in contrast, rapamycin stimulated mTOR complex 2 substrate AKT(Ser473) phosphorylation although it inhibited mTOR complex 1 substrate S6K phosphorylation. PKI-587, as a single agent, stimulated MEK and ERK phosphorylation. However, when PKI-587 and sorafenib were used in combination, they inhibited all the tested kinases in the Ras/Raf /MAPK and PI3K/AKT/mTOR pathways. CONCLUSION: The combination of PKI-587 and sorafenib has the advantage over monodrug therapy on inhibition of HCC cell proliferation by blocking both PI3K/AKT/mTOR and Ras/Raf/MAPK signaling pathways.

Predictors of surgical site infection after liver resection: a multicentre analysis using National Surgical Quality Improvement Program data.

BACKGROUND: Postoperative infections are frequent complications after liver resection and have significant impact on length of stay, morbidity and mortality. Surgical site infection (SSI) is the most common nosocomial infection in surgical patients, accounting for 38% of all such infections. OBJECTIVES: This study aimed to identify predictors of SSI and organ space SSI after liver resection. METHODS: Data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for patients who underwent liver resection in 2005, 2006 or 2007 in any of 173 hospitals throughout the USA were analysed. All patients who underwent a segmental resection, left hepatectomy, right hepatectomy or trisectionectomy were included. RESULTS: The ACS-NSQIP database contained 2332 patients who underwent hepatectomy during 2005-2007. Rates of SSI varied significantly across primary procedures, ranging from 9.7% in segmental resection patients to 18.3% in trisectionectomy patients. A preoperative open wound, hypernatraemia, hypoalbuminaemia, elevated serum bilirubin, dialysis and longer operative time were independent predictors for SSI and for organ space SSI. CONCLUSIONS: These findings may contribute towards the identification of patients at risk for SSI and the development of strategies to reduce the incidence of SSI and subsequent costs after liver resection.

Massive Leiomyomatous Uterine Proliferation Following Kidney Transplantation: A Case Report and Literature Review.

Uterine fibroids are the most common benign uterine tumors affecting > 50% of premenopausal women. The incidence, burden and symptoms from uterine fibroids are higher in women of African descent compared to Caucasians. Despite increasing number of African American females being evaluated for and undergoing kidney transplantation (KT), perioperative management guidelines for uterine fibroids currently do not exist. We present a case of a 40 y/o African American female with known symptomatic uterine fibroids preoperatively and medically managed, who underwent a successful KT and 4 years later progressively developed massive leiomyomatous uterine proliferation, causing a complete lateral displacement of the transplanted kidney with severe hydronephrosis, transplant ureteral obstruction and secondary urinary tract infections with bacteremia. This obstruction required a percutaneous nephrostomy tube placement followed by an interval transabdominal hysterectomy, which was complicated by transplant ureteral transection requiring ureteral reimplantation, resulting in prolonged hospitalization, follow-up and outpatient antibiotic regimen. There is a need for management guidelines for uterine fibroids incidentally encountered during the KT evaluation process to avoid similar preventable post-KT complications in patient populations most commonly affected. Literature review and perioperative management/surveillance strategies are provided.

QT prolongation is associated with increased mortality in end stage liver disease.

AIM: To determine the prevalence of QT prolongation in a large series of end stage liver disease (ESLD) patients and its association to clinical variables and mortality. METHODS: The QT interval was measured and corrected for heart rate for each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females. Multiple clinical variables were evaluated including sex, age, serum sodium, international normalized ratio, creatinine, total bilirubin, beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology of liver disease. RESULTS: Among 406 ESLD patients analyzed, 207 (51.0%) had QT prolongation. The only clinical variable associated with QT prolongation was male gender (OR = 3.04, 95%CI: 2.01-4.60, P < 0.001). During the study period, 187 patients (46.1%) died. QT prolongation was a significant independent predictor of mortality (OR = 1.69, 95%CI: 1.03-2.77, P = 0.039). In addition, mortality was also associated with viral etiology of ESLD, elevated MELD score and its components (P < 0.05 for all). No significant reversibility in the QT interval was seen after liver transplantation. CONCLUSION: QT prolongation was commonly encountered in an ESLD population, especially in males, and served as a strong independent marker for increased mortality in ESLD patients.

Revisiting lithium-associated hyperparathyroidism in the era of intraoperative parathyroid hormone monitoring.

BACKGROUND: Chronic lithium therapy may cause hyperparathyroidism (HPT). The utility of intraoperative parathyroid hormone monitoring (IOPTH) in these patients is unknown. The authors' hypothesis was that multiglandular disease is more common in these patients, and the ability of IOPTH to predict cure may be limited. METHODS: Twelve patients had HPT during chronic lithium therapy and underwent parathyroidectomy with IOPTH. Criteria for curative resection were a decrease > or =50% from baseline and into the normal range. Calcium and PTH levels were measured during follow-up. RESULTS: Preoperatively, mean calcium was 11.0 +/- 0.1 mg/dL, and PTH was 116 +/- 14 pg/mL. Fifty percent of patients had multiglandular disease confirmed by IOPTH levels. Mean IOPTH decrease from baseline was 74 +/- 4%. Although 10 of 12 patients met criteria for curative resection, only 8 remain normocalcemic. The 2 patients who did not meet criteria remain normocalcemic. Mean postoperative calcium for all patients was 9.5 +/- 0.2 mg/dL. Of the 10 normocalcemic patients, 4 also have hyperparathormonemia (mean PTH, 119 +/- 19 pg/mL). CONCLUSIONS: The incidence of multiglandular disease in HPT after chronic lithium exposure is higher than standard HPT. The ability of IOPTH to predict durable normocalcemia is limited. Bilateral neck exploration should be considered for these patients regardless of whether IOPTH monitoring is used.

Resection of pulmonary metastasis from parathyroid carcinoma.

The management of metastasis from parathyroid carcinoma (PC) is an unusual challenge. Systemic therapy has minimal effect on the course of the disease and its associated hypercalcemia. Resection of isolated pulmonary metastases is an attractive option in the setting of recurrent hypercalcemia. We report a case of a patient who underwent resection of multiple functional PC pulmonary metastases almost 20 years after the original neck resection. The patient originally presented in 1982 with what was thought to be hyperparathyroidism secondary to a parathyroid adenoma. Surgical exploration revealed the presence of a well differentiated PC. The patient was transiently normocalcemic, but underwent surgical exploration in 1993 and 1996 for recurrent PC in the neck. The patient again improved, but presented in 2001 with diffuse arthralgia, fatigue, malaise, weight loss, and decreased appetite. She was found to have a serum calcium of 12.7 mg/dL and an intact parathyroid hormone of 1542 pmol/L. Computed tomography identified the presence of two right-sided and two left-sided pulmonary masses. Sternotomy with bilateral pulmonary metastectomy was performed. Functional PC metastasis was confirmed on pathological examination. One year following metastectomy the patient is hypocalcemic, requiring oral calcium and vitamin D supplementation. Functional pulmonary metastasis from PC is a rare cause of hypercalcemia. Complete resection of isolated pulmonary metastases can provide effective palliation with long-term survival.

The role of PI3K/mTOR inhibition in combination with sorafenib in hepatocellular carcinoma treatment.

BACKGROUND: Deregulated RAS/RAF/MAPK and PI3K/AKT/mTOR signaling pathways are found in hepatocellular carcinoma (HCC). This study aimed to test the inhibitory effects of PI-103 (a small molecule inhibitor of PI3K and mTOR) and sorafenib as single agents and in combination on HCC tumorigenesis in an in vivo xenograft model. MATERIALS AND METHODS: In vitro study: Huh7 proliferation was assayed by 3H-thymidine incorporation and by thiazolyl blue tetrazolium bromide (MTT) assay. Western blots were used to detect phosphorylation of the key enzymes in the two pathways. In vivo study: Human HCC cell line Huh7 was inoculated into nude mice s.c. and the mice were treated with sorafenib (20 mg/kg/day) and PI-103 (5 mg/kg, every 4 days). Tumor size was measured every other day. Tumors were isolated for western blot and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay detection of apoptosis and signaling pathway enzymes. RESULTS: Our in vitro study found that combination of sorafenib and PI-103 additively inhibited Huh7 proliferation as compared to single-agent treatment. Sorafenib and PI-103 as single agents differentially inhibited or activated key enzymes (MEK, ERK, AKT, mTOR, and S6K) in PI3K/AKT/mTOR and RAS/RAF/MAPK signaling pathways. Combination of sorafenib and PI-103 inhibited all the key enzymes in the two pathways. Our in vivo study demonstrated significant differences between control group, mono-drug groups and drug-combination group (p<0.05). Combination of Sorafenib and PI-103 more efficiently inhibited tumorigenesis as compared to mono-drug treatments (p<0.032). CONCLUSION: The combination of PI-103 and sorafenib has the advantage over mono-drug therapy on inhibition of HCC cell proliferation and tumorigenesis by inhibiting both PI3K/AKT/mTOR and RAS/RAF/MAPK signaling pathways.

Liver transplantation for the treatment of liver metastases from neuroendocrine tumors: an analysis of the UNOS database.

OBJECTIVE: To determine outcomes in patients undergoing liver transplantation (LT) for metastatic neuroendocrine tumors (NETs). DESIGN: Retrospective analysis. SETTING: University of Kentucky Medical Center. PATIENTS: Patients undergoing LT performed for NET metastases from October 1, 1988, through January 31, 2008, were analyzed using the United Network for Organ Sharing database. Main Outcome Measure  Patient survival. RESULTS: During the study period, 87 280 LTs were performed. One hundred fifty LTs were performed for metastatic NETs. Among those 150 patients undergoing LT, 51 patients (34.0%) had carcinoid, 6 had insulinoma (4.0%), 3 had glucagonoma (2.0%), 11 had gastrinoma (7.3%), and 9 had vasoactive intestinal peptide-secreting tumors (6.0%); an additional 70 (46.7%) had an unspecified NET. The mean (SE) age of the patients was 45.1 (12.5) years. The mean (SE) cold ischemic time was 8.9 (4.1) hours. One hundred forty-four patients were adults and 6 were children. Thirteen patients received another organ at the time of LT. During the same period, 4693 patients underwent transplantation for hepatocellular carcinoma. Overall, 1-, 3-, and 5-year survival rates for patients with NETs undergoing isolated LT were 81%, 65%, and 49%, respectively. No difference in survival was observed in patients with carcinoid vs noncarcinoid tumors (P = .84). No significant difference was observed in patient survival between those with metastatic NETs and those with hepatocellular carcinoma. Patients waiting for LT longer than 2 months had improved survival (P = .005). CONCLUSIONS: Patients with liver metastases from NETs who were undergoing LT had long-term survival similar to that of patients with hepatocellular carcinoma. Longer wait times were associated with better outcomes in our series. Waiting for disease to stabilize before considering patients with liver metastases from NETs for transplantation may be appropriate. Excellent results can be obtained in highly selected patients.

PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways.

BACKGROUND: Aberrant Ras/Raf/MAPK and PI3K/AKT/mTOR signaling pathways are found in hepatocellular carcinoma (HCC). This study reports how sorafenib (a multi-kinase inhibitor) and PI-103 (a dual PI3K/mTOR inhibitor) alone and in combination inhibit the proliferation of the HCC cell line, Huh7. MATERIALS AND METHODS: Huh7 proliferation was assayed by 3H-thymidine incorporation and by MTT assay. Western blot was used to detect phosphorylation of the key enzymes in the Ras/Raf and PI3K pathways. RESULTS: Sorafenib and PI-103, as single agents inhibited Huh7 proliferation and epidermal growth factor (EGF)-stimulated Huh7 proliferation in a dose-dependent fashion; the combination of sorafenib and PI-103 produced synergistic effects. EGF increased phosphorylation of MEK and ERK, key Ras/Raf downstream signaling proteins; this activation was inhibited by sorafenib. However, sorafenib as a single agent increased AKT(Ser473) and mTOR phosphorylation. EGF-stimulated activation of PI3K/AKT/mTOR pathway components was inhibited by PI-103. PI-103 is a potent inhibitor of AKT(Ser473) phosphorylation; in contrast, rapamycin stimulated AKT(Ser473) phosphorylation. It was found that PI-103, as a single agent, stimulated MEK and ERK phosphorylation. However, the combination of sorafenib and PI-103 caused inhibition of all the tested kinases in the Ras/Raf and PI3K pathways. CONCLUSION: The combination of sorafenib and PI-103 can significantly inhibit EGF-stimulated Huh7 proliferation by blocking both Ras/Raf/MAPK and PI3K/AKT/mTOR pathways.

Appendiceal neoplasms with peritoneal dissemination: outcomes after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy.

BACKGROUND: Appendiceal neoplasms frequently present with peritoneal dissemination (PD) and have a clinical course marked by bowel obstruction and subsequent death. Few data have correlated outcome with appendiceal histology after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC). We have reviewed our experience with cytoreductive surgery and IPHC for PD from the appendix. METHODS: A total of 110 cases of PD from proven appendiceal neoplasms treated with IPHC were identified from a prospectively managed database. Tumor samples were classified on pathologic review as disseminated peritoneal adenomucinosis (n = 55), peritoneal mucinous carcinomatosis (PMCA) with intermediate features (n = 18), PMCA (n = 29), or high-grade nonmucinous lesions (n = 8). A retrospective review was performed with long-term survival as the primary outcome measure. RESULTS: A total of 116 IPHCs were performed on 110 patients for appendiceal PD between 1993 and 2004. The 1-, 3-, and 5-year survival rates for all cases were 79.9% +/- 4.1%, 59.0% +/- 5.7%, and 53.4% +/- 6.5%, respectively. When stratified by histology, disseminated peritoneal adenomucinosis and intermediate tumors had better 3-year survival rates (77% +/- 7% and 81% +/- 10%) than PMCA and high-grade nonmucinous lesions (35% +/- 10% and 15% +/- 14%; P = .0032 for test of differences between groups). Age at presentation (P = .0134), performance status (P < .0001), time between diagnosis and IPHC (P = .0011), resection status (P = .0044), and length of hyperthermic chemoperfusion (P = .0193) were independently associated with survival. CONCLUSIONS: The data show that long-term survival is anticipated in most patients who are treated with cytoreduction and IPHC for appendiceal PD. The findings presented herein underscore the important prognostic characteristics that predict outcome after IPHC in patients with PD. In all, this work establishes a framework for the consideration of IPHC in future trials for appendiceal PD.

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis from small bowel adenocarcinoma.

INTRODUCTION: Peritoneal carcinomatosis (PC) is associated with a dismal prognosis. Small bowel adenocarcinoma is a rare etiology for PC. Due to the rarity, poor prognosis, and lack of standard treatment, we chose to review our experience with this disease process treated with cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC). METHODS: From a prospective database of IPHC patients, six patients diagnosed with PC from adenocarcinoma of the small bowel were identified. Between 1995 and 2004 these patients underwent CS and IPHC with Mitomycin C. A retrospective review was performed on these patients with mortality as the primary outcome measure. RESULTS: Three of the six patients in this series are still alive, with a mean follow-up of 19.7 months after treatment with CS and IPHC. Three patients died of disease progression 29, 30, and 45 months after IPHC. Median survival after diagnosis of small bowel adenocarcinoma was 54 months, while median survival after CS and IPHC for PC was 30.1 months. CONCLUSIONS: Small bowel adenocarcinoma with PC remains an unusual therapeutic challenge. Treatment with CS and IPHC is an attractive option for patients in this setting.

Renovascular disease in children and adolescents.

PURPOSE: This retrospective review describes the surgical management of renovascular disease in 25 consecutive children and adolescents with severe hypertension. METHODS: Patients 95 th percentile systolic or diastolic pressure adjusted for gender, age, and height). RA repair comprised 25 bypasses (73%) consisting of 28% saphenous vein, 60% hypogastric artery, and 12% polytetrafluoroethylene; 2 patch angioplasties (6%), and 7 reimplantations (21%). Branch RA exposure was required in 28 kidneys (88%), and branch reconstruction was required in 61%. Warm in situ repair was used in 53%, in situ cold perfusion in 24%, and ex vivo cold perfusion in 23%. Of six bilateral RA repairs, one was staged and two patients are awaiting a staged repair. Combined aortic reconstruction was required in three patients. No unplanned nephrectomy was performed. There were no perioperative deaths. Hypertension was cured in 36%, improved in 56%, and failed in 8% at mean follow-up of 46.4 +/- 7.8 months. The mean calculated glomerular filtration rate increased from 82.0 mL/min/1.73 m 2 preoperatively to 98.2 mL/min/1.73 m 2 postoperatively. The postoperative patency of 30 RA reconstructions was evaluated by angiography, RDS scanning, or both. At mean follow-up of 32.8 months (median, 21.2 months), primary RA patency was 91%. No failures were observed after 2 months follow-up. Estimated survival was 100% at 60 months, with one death 9 years after surgery. CONCLUSIONS: Renovascular hypertension in children and adolescents was caused by a heterogeneous group of lesions. All patients had RA repair, with arterial autografts in most of the RA bypasses. Cold perfusion preservation was used in half of the complex branch RA repairs. These strategies provided 91% primary patency at mean follow-up of 32.8 months, with beneficial blood pressure response in 92%. Surgical repair of clinically significant renovascular disease in children and adolescents is supported by these results.